Jacobsen syndrome, also known as 11q deletion disorder, is a rare genetic disorder caused by a deletion on the long arm of chromosome 11. The size of the deletion varies among affected individuals, but it typically includes the end of the long arm of chromosome 11 (11q). Jacobsen syndrome is a serious disorder that affects many parts of the body and can cause intellectual disability, heart defects, bleeding problems, skeletal abnormalities, kidney problems, and frequent infections during infancy. However, with early diagnosis and proper medical care, many people with Jacobsen syndrome can have improved health and development.
What is Jacobsen syndrome?
Jacobsen syndrome is named after Petra Jacobsen, who first described the disorder in 1973 after observing a cluster of patients with similar patterns of physical abnormalities and intellectual disability. It is caused by a deletion of genes on the q arm of chromosome 11. The deletion occurs sporadically during the formation of reproductive cells (eggs and sperm) in a parent, or in early fetal development. Jacobsen syndrome is considered to be rare, occurring in around 1 in 100,000 newborns. However, the condition may be underdiagnosed because the physical features can be subtle.
Characteristics
The most common features of Jacobsen syndrome include:
- Growth delay before and after birth
- Intellectual disability, ranging from mild to severe
- Distinctive facial features, including a small head, low-set ears, wide-set eyes, and a thin upper lip
- Heart defects, such as ventricular septal defect, atrial septal defect, or hypoplastic left heart
- Skeletal abnormalities, particularly of the hands and feet
- Low platelet count (thrombocytopenia), which can lead to easy bruising and bleeding
- Kidney problems, like congenital absence of one kidney
- Recurrent infections during infancy
The severity of symptoms can vary widely among affected individuals depending on the size and location of the chromosome deletion. People with larger deletions tend to have more severe intellectual disabilities and physical defects.
Diagnosis
Jacobsen syndrome is suspected if a child has the characteristic pattern of physical abnormalities, growth delay, and developmental delay. Diagnosis is confirmed through genetic testing, such as chromosome analysis or chromosomal microarray, which can identify the deletion on the long arm of chromosome 11. Prenatal testing is possible if the disorder is detected on a prenatal ultrasound or if there is a known familial deletion.
Treatment
There is no cure for Jacobsen syndrome because the genetic defect cannot be repaired. However, the aim of treatment is to manage the symptoms and associated health problems to improve the child’s overall quality of life and functioning. A multidisciplinary approach involving a variety of medical specialists is recommended.
- Monitoring growth and nutritional intake
- Physical, occupational, and speech therapy
- Educational support services
- Medications to manage bleeding problems or heart defects
- Surgery to correct heart defects, spinal curvature, or other physical abnormalities
Early intervention programs are important to foster cognitive, motor, and social development. As the child grows, additional resources may be needed to address learning disabilities, behavioral issues, and vocational training needs.
Is Jacobsen syndrome fatal?
The short answer is that Jacobsen syndrome is not always fatal. With comprehensive medical care and proper treatment of associated health problems, many individuals with Jacobsen syndrome can survive well into adulthood. However, there are some serious medical concerns that can be life-threatening if not managed properly.
Heart defects
Around 80% of people with Jacobsen syndrome are born with a congenital heart defect. The most common defects include ventricular septal defect (hole in the wall between the ventricles), atrial septal defect (hole between the atria), and left-sided heart obstructive defects. More severe defects like hypoplastic left heart syndrome are less common but can be life-threatening if not treated with surgery soon after birth. Even after corrective surgery, people with complex congenital heart defects may continue to have serious cardiovascular problems throughout life.
Bleeding disorders
Low platelet counts (thrombocytopenia) affect the majority of people with Jacobsen syndrome and can range from mild to severe. In the most severe cases, dangerous internal bleeding can occur spontaneously or after minor trauma. To help prevent serious bleeding episodes, medications can be used to boost platelet production, or transfusions of platelets may be needed before surgeries. Avoidance of medications that impede clotting is also important.
Recurrent infections
Because of their compromised immune systems, infants with Jacobsen syndrome are prone to recurrent bacterial and viral infections. This includes respiratory infections like pneumonia, urinary tract infections, meningitis, and gastroenteritis. Without prompt treatment, severe infections can quickly become life-threatening in babies. However, the issue of infections often improves with age as the child’s immune function matures.
Kidney dysfunction
Kidney anomalies like a solitary kidney, duplication of the collecting system, or vesicoureteral reflux are seen in around one-third of people with Jacobsen syndrome. Kidney dysfunction can lead to problems with urinary tract infections, incontinence, and improper filtering of the blood. Progressive worsening of kidney function can develop over time, eventually leading to renal failure in some cases. Regular checkups to monitor kidney health are recommended.
Mortality rate
There are limited long-term survival statistics available specifically for Jacobsen syndrome. Estimates indicate that the first year of life poses the highest mortality risk for infants with Jacobsen syndrome, ranging from 9-30%. The most common causes of death in the first year are congenital heart disease and bleeding disorders.
With improved medical care over the past decades including antibiotics, transfusions, and advances in pediatric cardiology, survival has improved significantly. Recent studies show that 70-80% of affected children survive to adulthood. However, life expectancy remains reduced compared to the general population. The frequency of serious heart defects, risk of recurrent infections, potential for kidney failure, and higher incidence of certain cancers (leukemia, lymphoma) contribute to the reduced life span.
Factors affecting life expectancy
The life expectancy for individuals with Jacobsen syndrome depends on the severity of the particular deletion and associated medical problems. Some of the key factors that impact survival include:
- Presence and complexity of congenital heart defect
- Severity of bleeding disorder
- Extent of kidney dysfunction
- Degree of intellectual disability and self-care abilities
- Frequency of serious infections
- Quality of medical care available
For patients with less severe defects and medical issues, life expectancy may be closer to normal. But for those with serious complications like complex congenital heart disease, kidney failure, immune deficiency, or significant intellectual impairment, lifespan may be substantially reduced. Ongoing care by a team of specialists helps optimize health and longevity.
Quality of life
While Jacobsen syndrome is a serious disorder, many affected individuals can have good quality of life with proper education, social support, and medical care. Physical and intellectual impairments cover a wide spectrum, so functioning depends largely on an individual’s abilities. Some key points regarding quality of life include:
- Early intervention services improve development and independence.
- Inclusive educational settings and vocational training tailored to abilities can promote success.
- Assistive technologies can help mitigate mobility, communication, and learning challenges.
- Outpatient monitoring and treatment by specialists prevents health emergencies.
- Counseling and peer support groups empower patients and families.
- Home healthcare services can support activities of daily living.
With family support, social integration, and self-advocacy, many people with Jacobsen syndrome can enrich their lives and participate meaningfully within their communities. Although ongoing medical care is needed, focusing on each patient’s capabilities can have profound benefits on their health, socialization, and happiness.
Conclusion
Jacobsen syndrome is a rare chromosomal disorder that can cause intellectual disability, physical abnormalities, and serious medical problems affecting the heart, blood, kidneys, and immune system. If left untreated, complications of Jacobsen syndrome can be fatal, especially in infancy and early childhood when the medical issues are most acute. However, with comprehensive medical care by a specialized team, preventative treatments, and diligent monitoring, the majority of affected children can survive well into adulthood.
While Jacobsen syndrome does reduce average life expectancy, patients have a wide range of outcomes depending on their symptom severity. Ongoing care focusing on each patient’s strengths and capabilities allows many individuals with Jacobsen syndrome to live productive and satisfying lives within their families and communities. Research continues to advance clinical knowledge about this rare disorder and develop novel targeted therapies that will improve care in the future.
References
- Jacobsen Syndrome Foundation Inc. About Jacobsen Syndrome. https://www.jacobsensyndrome.org/about-jacobsen-syndrome/. Accessed March 2022.
- Rare Chromosome Disorder Support Group, Chromosome 11 Deletion Support Group. Handbook on Jacobsen Syndrome (11q-) for families and healthcare professionals. http://www.rarechromo.org/information/Chromosome%2011/Jacobsen%20Syndrome%20FtNW.pdf. Published 2012. Accessed March 2022.
- Grossfeld PD, Mattina T, Lai Z, et al. The 11q terminal deletion disorder: a prospective study of 110 cases. Am J Med Genet A. 2004;129A(1):51-61.
- Penny LA, Dell’Aquila M, Jones MC, et al. Clinical and molecular characterization of patients with distal 11q deletions. Am J Hum Genet. 1995;56(3):676-683.
- Moeschler JB, Dallaire S, Brewer C, et al. Medical management of genetic syndromes: Jacobsen syndrome. Am J Med Genet A. 2015;167A(12):2975-2981.